Biochemical approaches will be applied to study the mechanism of myelin formation and to determine the regulatory controls affecting myelin metabolism during development and adulthood. The biochemical events that occur in the demyelination processes will be also investigated. The turnover of individual molecular-species of complex-lipids such as sphingomyelins, cerebrosides and sulfatides in myelin and microsomal membranes will be investigated by employing high performance liquid chromatography (HPLC) technique to obtain information on the relationship between metabolic activity and acyl group composition of these lipids. The origin of lipids in myelin membranes remains unknown. In vivo metabolic studies have suggested that intracellular transport and/or exchange of newly synthesized lipids from endoplasmic reticulum (microsomes) to myelin can occur with lipo-protein carriers as intermediates. Studies are planned to evaluate the exchange and transport of individual phospholipids, cholesterol and sphingolipids between rat brain microsomal, myelin, 'myelin-like' and other related subcellular membranes in vitro. The role of soluble proteins which stimulate such exchange will be studied. The physiological significance of the subfractions of myelin and 'myelin-like' membranes in the process of myelination will be investigated. The role of the enzyme UDP-galactose: ceramide galactosyltransferase, found in the myeline subfractions during development, will be determined in the process of initiation and regulation of myelin assembly. HPLC technique will be employed to determine accumulation of psychosine in Krabbe's disease and sphingomyeline metabolism in Niemann-Picks disease. The possible role of psychoisne as an intermediate in the biosynthesis of cerebrosides in vivo will be evaluated.